Penicillin: Function, history, and resistance (original) (raw)

Penicillins are a group of antibacterial drugs that attack a wide range of bacteria. They were the first drugs of this type that doctors used. These drugs have saved millions of lives.

Penicillium fungi are the source of penicillin, which people can take orally or via injection.

People across the globe now widely use penicillins to treat infections and diseases.

• Penicillins were the first antibiotic that doctors used.
• There are several antibiotics in the penicillin class.
• Experts credit Alexander Fleming with discovering penicillins.
• Penicillin works by interfering with bacteria cell walls.
• Less than 1 percent of people are dangerously allergic to penicillin.

Drugs in the penicillin class work by indirectly bursting bacterial cell walls. They do this by acting directly on peptidoglycans, which play an essential structural role in bacterial cells.

Peptidoglycans create a mesh-like structure around the plasma membrane of bacterial cells, which increases the strength of the cell walls and prevents external fluids and particles from entering the cell.

When a bacterium multiplies, small holes open up in its cell walls as the cells divide. Newly-produced peptidoglycans then fill these holes to reconstruct the walls.

Penicillins block the protein struts that link the peptidoglycans together. This prevents the bacterium from closing the holes in its cell walls.

As the water concentration of the surrounding fluid is higher than that inside the bacterium, water rushes through the holes into the cell and the bacterium bursts.

People generally attribute the discovery of penicillins to Alexander Fleming. The story goes that he returned to his laboratory one day in September 1928 to find a Petri dish containing Staphylococcus bacteria with its lid no longer in place.

The dish had become contaminated with a blue-green mold called Penicillium notatum. Fleming noted that there was a clear ring surrounding the mold where the bacteria had been unable to grow.

By discovering this mold and recognizing its use, Fleming set the wheels in motion to create one of the most useful drugs in medical history.

In March 1942, Anne Miller became the first civilian to receive successful treatment with penicillin. She narrowly avoided death following severe infection after a miscarriage.

Although Fleming technically discovered the first antibiotic, scientists had to do a lot of work before penicillins could become available for general use.

Scientists with a superior laboratory and a deeper understanding of chemistry than Fleming carried out the bulk of the work. Howard Florey, Norman Heatley, and Ernst Chain performed the first in-depth and focused studies on the drug.

In Fleming’s Nobel Prize acceptance speech, he warned that the overuse of penicillins might, one day, lead to bacterial resistance. This has since become a problem.

Contrary to popular opinion, it is not the person who develops resistance to penicillins but the bacteria itself.

Bacteria have been around for billions of years. During this time, they have endured extreme environments and, as a result, are highly adaptable. They also regenerate very rapidly, making relatively quick genetic changes possible across a population.

There are three common ways in which bacteria can develop an immunity to penicillin:

• Penicillinase: Bacteria are sometimes able to produce penicillinase, an enzyme that degrades penicillins. This ability can spread throughout the bacterial population via a small ring of DNA in a process called conjugation. This is the bacterial equivalent of sexual reproduction, where individual organisms share new genetic information between them.
• Altered bacterial structure: Some bacteria can subtly change the format of the penicillin-binding proteins in their peptidoglycan wall so that penicillins can no longer bind to it.
• Penicillin removal: Other bacteria develop systems to export penicillins. Bacteria have efflux pumps that they use to release substances from the cell. The repurposing of some of these pumps can allow the cell to dispose of penicillins.

The most commmon side effects of taking penicillins include:

• diarrhea
• nausea
• a headache
• skin rashes and hives

Less common side effects include:

• shortness of breath or irregular breathing
• joint pain
• sudden lightheadedness and fainting
• puffiness and redness of the face
• scaly, red skin
• vaginal itching and discharge, due to either a yeast infection or bacterial vaginosis
• sore mouth and tongue, sometimes with white patches
• abdominal cramps, spasms, tenderness, or pain

Rare side effects include:

• anxiety, fear, or confusion
• a sense of impending doom
• hallucinations
• yellowing of the eyes and skin
• a sore throat
• unusual bleeding
• diarrhea and reduced urination
• convulsions

Although the use of penicillins is widespread, some issues or contraindications can occur, as with any drug:

• Breast-feeding: People who are breast-feeding may pass small amounts of penicillin to the child. This can result in the child experiencing allergic reactions, diarrhea, fungal infections, and skin rash.
• Interactions: Some other drugs can interact with penicillins. Checking with a doctor before taking multiple medications is vital.
• Bleeding problems: Some penicillins, such as carbenicillin, piperacillin, and ticarcillin, can make pre-existing bleeding problems worse.
• Oral contraceptives: Penicillins can interfere with birth control pills, increasing the risk of unwanted pregnancy.
• Cystic fibrosis: People with cystic fibrosis are more prone to fever and skin rashes when taking piperacillin.
• Kidney disease: Individuals with kidney disease have an increased risk of side effects.
• Methotrexate: Methotrexate disrupts cell growth and can treat several conditions, including leukemia and some autoimmune diseases. Penicillins prevent the body from disposing of this drug, potentially leading to severe complications.
• Phenylketonuria: Some stronger, chewable amoxicillin tablets contain high levels of aspartame that the body converts to phenylalanine. This is dangerous for anyone with phenylketonuria.
• Gastrointestinal problems: Patients with a history of stomach ulcers or other intestinal diseases might be more likely to develop colitis when taking penicillins.

Penicillin allergy

Some people have an allergy to penicillins.

Allergic reactions to penicillin typically lead to hives, wheezing, and swelling, particularly of the face.

Around 10 percent of people report an allergy to penicillins but the real figure is closer to 1 percent, and only around 0.03 percent exhibit life-threatening allergic responses.

Alcohol and penicillin

Certain antibiotics, such as metronidazole and tinidazole, have severe reactions with alcohol. However, this is not the case with penicillins.

Penicillins have saved countless lives throughout their history of use in medicine. However, doctors are now worried about the increase in antibiotic resistance. Only time will tell how the antibiotics of the future will overcome this hurdle.